Gluten and subtle gut changes in non-coeliac gluten sensitivity
What it found
In gut biopsies from people with non-coeliac gluten sensitivity, the villi were shorter and crypts deeper than in people without gluten problems, even when the tissue looked normal under the microscope.
The changes were milder than in coeliac disease.
What they found
Studies in people
Villus height
Villi were shorter in people with non-coeliac gluten sensitivity than in controls, even in those whose biopsies looked normal (Marsh 0). In those with mild tissue damage (Marsh I-II), villus height was similar to coeliac disease.
Crypt depth
Crypts were deeper in non-coeliac gluten sensitivity than in controls, even in Marsh 0 cases. Crypt depth was similar to coeliac disease.
Villus-to-crypt ratio
The villus-to-crypt ratio was lower in non-coeliac gluten sensitivity than in controls, even in Marsh 0 cases. It was higher than in coeliac disease.
Immune cells in villi
A type of immune cell (intraepithelial lymphocytes) was more numerous in the villi of people with non-coeliac gluten sensitivity than in controls, but less numerous than in coeliac disease. In Marsh 0 cases, the counts were still higher than controls.
Immune cells in crypts
Immune cell counts in the crypts of people with non-coeliac gluten sensitivity were similar to controls but lower than in coeliac disease.
Eosinophils
A type of immune cell called eosinophils in the gut lining was similar in non-coeliac gluten sensitivity and controls, and lower than in coeliac disease. The authors say this cell type does not appear useful for diagnosis.
What the authors conclude
“NCGS duodenal mucosa exhibits distinctive changes consistent with an intestinal response to luminal antigens, even at the Marsh 0 stage of villus architecture.”
Also in their conclusions
- They conclude that the gut lining in non-coeliac gluten sensitivity shows changes consistent with an immune response to gluten, even when the tissue looks normal (Marsh 0).
- They advise that the range of what is considered normal gut tissue needs to be refined to distinguish it from the subtle changes of non-coeliac gluten sensitivity and coeliac disease.
- They state that a diagnosis of non-coeliac gluten sensitivity based only on tissue appearance would be inaccurate, and that better diagnostic markers are needed.
How it was done
The authors say the tissue changes caused by gluten in people with non-coeliac gluten sensitivity are poorly defined, and it is unclear whether these patients can have normal or nearly normal gut tissue.
They examined stored gut biopsy slides from 698 people: 175 with non-coeliac gluten sensitivity, 261 with coeliac disease, and 262 controls, from 9 countries. They measured villus height, crypt depth, their ratio, and immune cells in the gut lining.
What it can’t tell you
- This study looked at stored biopsy slides, so it cannot show whether gluten caused these changes or whether they would change over time.
- The people in the study already had symptoms and were diagnosed with non-coeliac gluten sensitivity or coeliac disease, so the findings may not apply to everyone.
- The study cannot show how these tissue changes relate to symptoms or long-term health.
Who paid
- Funding
- Funded by NCI NIH HHS (from the PubMed record).
- Conflicts
- The authors declare no conflict of interest.
- Authors work at
- Milton Keynes University Hospital, UK; Ankara University Medical School, Turkey; University of Oxford, UK
The paper
- Title
- Gluten Induces Subtle Histological Changes in Duodenal Mucosa of Patients with Non-Coeliac Gluten Sensitivity: A Multicentre Study
- Type
- Study
- Evidence
- Studies in people
- Summarised from
- Full text
- Cite
- Rostami K, Ensari A, Marsh MN, et al (2022). Gluten Induces Subtle Histological Changes in Duodenal Mucosa of Patients with Non-Coeliac Gluten Sensitivity: A Multicentre Study. Nutrients. doi:10.3390/nu14122487Free full textPubMed 35745217DOI
Summary written 26 Sep 2026. Check it against the paper before it changes what you eat. How we summarise papers · Report an error